May 20, 2019

Anti-cancer effect of marchantin C via inducing lung cancer cellular senescence associated with less secretory phenotype

Biochimica Et Biophysica Acta. General Subjects
Xiu-Lei ZhangHui-Qing Yuan

Abstract

Lung cancer is the leading cause of global cancer deaths. Current chemotherapeutic agents for lung cancer treatment are generally accompanied with severe side effects. Here, we report that marchantin C (Mar-C), a potential natural compound with little chemotherapeutic toxicity, exerts a well anti-tumor effect against lung cancer via inducing cellular senescence. The antitumor activity of Mar-C was evaluated by MTT and colony formation in vitro cytotoxicity assays, and xenograft and homograft in vivo model. Antitumor mechanisms of Mar-C were investigated through SA-β-gal staining, Q-PCR, immunoblotting, immunofluorescence, protein array and siRNA knocking-down analysis. Mar-C selectively induces senescence of lung cancer cells with limited cytotoxicity on normal or non-neoplastic cells. Mar-C-induced senescence was associated with the elevation of ROS and activation of DNA-damage, and largely dependent of prolonged p21CIP1 accumulation. The senescence-associated secretory phenotype (SASP) induced by Mar-C was distinct from doxorubicin-induced. Furthermore, Mar-C exhibited an inhibitory activity on tumor growth with little toxicity in animal studies, and significantly prolonged the survival time of tumor-bearing mice than that of...Continue Reading

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Mentioned in this Paper

Doxorubicin
Study
In Vivo
Immunofluorescence Assay
Cdkn1a protein, mouse
Sulfanilamide
Antineoplastic Agents
Cell Aging
Exertion
Cytotoxicity Assay

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